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WO2002074719A8 - Inhibitors of plasmepsins - Google Patents

Inhibitors of plasmepsins

Info

Publication number
WO2002074719A8
WO2002074719A8 PCT/US2002/008024 US0208024W WO02074719A8 WO 2002074719 A8 WO2002074719 A8 WO 2002074719A8 US 0208024 W US0208024 W US 0208024W WO 02074719 A8 WO02074719 A8 WO 02074719A8
Authority
WO
WIPO (PCT)
Prior art keywords
plasmepsin
compounds
allophenylnorstatine
phenol
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2002/008024
Other languages
French (fr)
Other versions
WO2002074719A2 (en
WO2002074719A3 (en
Inventor
Ernesto Freire
Azin Nezami
Yoshiaki Kiso
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Johns Hopkins University
Original Assignee
Johns Hopkins University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Johns Hopkins University filed Critical Johns Hopkins University
Priority to US10/471,655 priority Critical patent/US7560482B2/en
Priority to AU2002306734A priority patent/AU2002306734A1/en
Publication of WO2002074719A2 publication Critical patent/WO2002074719A2/en
Publication of WO2002074719A8 publication Critical patent/WO2002074719A8/en
Anticipated expiration legal-status Critical
Publication of WO2002074719A3 publication Critical patent/WO2002074719A3/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Compounds and methods for the inhibition of anti-malarial target aspartyl protease plasmepsins (e.g. Plasmepsin I, Plasmepsin II, Plasmepsin IV and HAP) are provided. The compounds are based on allophenylnorstatine substituted at positions R1-R4, such that R1 is isoquinoline, carboxyl, naphtalene, phenyl, phenol, benzene, an amino acid, and derivatives thereof; R2 and R3 are aliphatic groups; and R4 is indan, naphthalene, benzylamine, phenyl, phenol, cyclopentane, tert-butylamine, or derivatives thereof. The compounds may be used to inhibit Plasmepsin II, to kill malarial parasites, and to treat malaria in a patient. Certain of the substituted allophenylnorstatine-based compounds also exhibit inhibitory activity against Cathepsin D.
PCT/US2002/008024 2001-03-15 2002-03-15 Inhibitors of plasmepsins Ceased WO2002074719A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US10/471,655 US7560482B2 (en) 2001-03-15 2002-03-15 Inhibitors of plasmepsins
AU2002306734A AU2002306734A1 (en) 2001-03-15 2002-03-15 Inhibitors of plasmepsins

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US27571301P 2001-03-15 2001-03-15
US60/275,713 2001-03-15

Publications (3)

Publication Number Publication Date
WO2002074719A2 WO2002074719A2 (en) 2002-09-26
WO2002074719A8 true WO2002074719A8 (en) 2003-03-13
WO2002074719A3 WO2002074719A3 (en) 2004-05-21

Family

ID=23053493

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/008024 Ceased WO2002074719A2 (en) 2001-03-15 2002-03-15 Inhibitors of plasmepsins

Country Status (3)

Country Link
US (1) US7560482B2 (en)
AU (1) AU2002306734A1 (en)
WO (1) WO2002074719A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8691831B2 (en) 2007-02-23 2014-04-08 Merck Sharp & Dohme Corp. Heterocyclic aspartyl protease inhibitors

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ547462A (en) 2003-12-15 2010-06-25 Schering Corp Heterocyclic aspartyl protease inhibitors
US7592348B2 (en) 2003-12-15 2009-09-22 Schering Corporation Heterocyclic aspartyl protease inhibitors
US7700603B2 (en) 2003-12-15 2010-04-20 Schering Corporation Heterocyclic aspartyl protease inhibitors
KR20080025079A (en) 2005-06-14 2008-03-19 쉐링 코포레이션 Aspartyl Protease Inhibitor
DE602006018456D1 (en) 2005-06-14 2011-01-05 Schering Corp PREPARATION AND USE OF COMPOUNDS AS ASPARTYL PROTEASE HEMMER
CN101193892A (en) 2005-06-14 2008-06-04 先灵公司 Macrocyclic heterocyclic aspartyl protease inhibitors
ES2436795T3 (en) 2005-06-14 2014-01-07 Merck Sharp & Dohme Corp. Aspartyl protease heterocyclic inhibitors, preparation and use thereof
CA2609582A1 (en) 2005-06-14 2006-12-28 Schering Corporation Aspartyl protease inhibitors
US8344058B2 (en) * 2005-08-26 2013-01-01 CID Centro de Investigación y Desarrollo Technológico S.A. de C.V. Reactive block copolymers as additives for the preparation of silicate-polymer composites
US7763606B2 (en) 2005-10-27 2010-07-27 Schering Corporation Heterocyclic aspartyl protease inhibitors
CA2672293A1 (en) 2006-12-12 2008-06-19 Schering Corporation Aspartyl protease inhibitors

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5734054A (en) 1996-11-05 1998-03-31 Pharmacopeia, Inc. Hydroxy-amino acid amides
US5962506A (en) * 1997-07-07 1999-10-05 Pharmacopeia, Inc. Glycol and hydroxyphosphonate peptidomimetics as inhibitors of aspartyl proteases
US5986102A (en) * 1998-04-29 1999-11-16 Pharmacopeia, Inc. Hydroxypropylamide peptidomimetics as inhibitors of aspartyl proteases

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8691831B2 (en) 2007-02-23 2014-04-08 Merck Sharp & Dohme Corp. Heterocyclic aspartyl protease inhibitors
US8691833B2 (en) 2007-02-23 2014-04-08 Merck Sharp & Dohme Corp. Heterocyclic aspartyl protease inhibitors

Also Published As

Publication number Publication date
WO2002074719A2 (en) 2002-09-26
US20050037953A1 (en) 2005-02-17
AU2002306734A1 (en) 2002-10-03
WO2002074719A3 (en) 2004-05-21
US7560482B2 (en) 2009-07-14

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